OPTIma:a tracking solution for proton computed tomography in high proton flux environments

Currently there is a large discrepancy between the currents that are used for treatments in proton beam therapy facilities and the ultra low beam currents required for many proton CT imaging systems. Here we provide details of the OPTIma silicon strip based tracking system, which has been designed for performing proton CT imaging in conditions closer to the high proton flux environments of modern spot scanning treatment facilities. Details on the physical design, sensor testing, modelling, and track reconstruction are provided along with Monte-Carlo simulation studies of the expected performance for proton beam currents of up to 50 pA at the nozzle when using a σ = ∼10 mm spot scanning cyclotron system. Using a detailed simulation of the proposed OPTIma system, a discrepancy of less than 1% on the Relative Stopping Power is found for various tissues when embedded within a 150 mm diameter Perspex sphere. It is found that by accepting up to 7 protons per bunch it is possible to operate at cyclotron beam currents up to 5 times higher than would be possible with a single proton based readout, significantly reducing the total beam time required to produce an image, while also reducing the discrepancy between the beam currents required for treatment and those used for proton CT

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

A scanning focussed vertical ion nanobeam: A new UK facility for cell irradiation and analysis

A new initiative to build a vertical scanning focussed nanobeam is outlined. This is a collaboration between the Gray Cancer Institute and the University of Surrey. The new beam line will operate in both single ion and full current modes and will enable the irradiation of single cells in vitro with precisely counted numbers of ions, it will also enable the analysis of cells in vitro. The beam will be focussed and scanned and should be capable of irradiating 100,000 cells per hour. A new end station will enable the cells to be irradiated in an environmentally controlled environment and will enable the cells to be imaged both on-line and off-line. The beam line will be housed in its own purpose built building, with the area around the end station comprising a biological clean room. © 2007 Elsevier B.V. All rights reserved

A scanning focused vertical ion nanobeam: A new UK facility for cell irradiation and analysis

A new initiative to build a vertical scanning focussed nanobeam is outlined. This is a collaboration between the Gray Cancer Institute and the University of Surrey. The new beam line will operate in both single ion and full current modes and will enable the irradiation of single cells in vitro with precisely counted numbers of ions, it will also enable the analysis of cells in vitro. The beam will be focussed and scanned and should be capable of irradiating 100,000 cells per hour. A new end station will enable the cells to be irradiated in an environmentally controlled environment and will enable the cells to be imaged both on-line and off-line. The beam line will be housed in its own purpose built building, with the area around the end station comprising a biological clean room. © 2007 Elsevier B.V. All rights reserved

Does the delivery technique impact the effect of respiratory motion in stereotactic ablative body radiotherapy?

Purpose/Objective: To examine whether the impact of respiratory motion on the delivered dose distributions for a range of tumour sizes in SABR, differs between 3DCRT,sliding window IMRT and RapidArc. Materials and Methods: Three patient data sets with different lung tumour sizes were selected: T1=6cc, T2=31cc and T3=60cc. Each was planned in Eclipse for SABR using 3DCRT, sliding window IMRT and VMAT, creating 9 treatment plans which were then delivered to a dynamic thorax phantom. The phantom was programmed to move at a typical patient breathing amplitude of 15mm with a period of 5 seconds and Varian linacs were used for the delivery. EBT3 Gafchromic film was used in coronal and sagittal planes for measuring dose distributions. Static phantom measurements were compared with the TPS calculated plans to establish agreement between expected and measured dose distributions without motion, using the software OmniPro I'mRT. Comparisons of static and dynamic phantom measurements followed. Global gamma analysis was used to carry out a relative comparison between the three delivery techniques. Five regions of the gamma index map (Middle, Proximal Left, Proximal Right, Distal Left, Distal Right) were analysed to quantify the differences along the axis of motion. The criteria used for the gamma analysis were 3%/3mm, with a threshold of 20%. Results: The setup and delivery accuracy was confirmed by the agreement between planned and static delivered dose distributions. The average percentage of pixels passing was 100% (T1),100% (T2) and 98.46% (T3). The comparison of films with and without motion gave lower percentages of pixels passing, ranging between 33.68 - 59.94% (T1), 47.86 - 61.77% (T2) and 43.44 - 64.32% (T3). Comparison of the delivery technique, showed passing rates of 33.63 - 52.25% (3DCRT), 43.44 - 64.52% (IMRT) and 46.58- 56.08% (VMAT). Analysis of the five regions for all delivery techniques gave averages of 93.76% (Middle), 58.7% (Proximal) and 12.8% (Distal). For 3DCRT results were 87.08% (Middle), 46.52% (Proximal) and 12.54% (Distal), for IMRT were 96.45%, 69.20%, 14.14% and for VMAT 97.75%, 60.39% and 11.71%, respectively. Conclusions: The results are indicative of the intra-fractional respiratory motion-induced dosimetric inaccuracies caused in three SABR delivery techniques.On average, the impact is greatest in the distal regions, significant in the proximal regions, whereas the middle region is less susceptible to these effects. No noticeable difference was observedbetween coronal and sagittal planes. The results also suggest that the effect of motion is greater in the proximal regions for 3DCRT in relation to the other techniques, particularly with smaller tumour sizes